P13498 (CY24A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cytochrome b-245 light chain

Alternative name(s):
Cytochrome b(558) alpha chain
Cytochrome b558 subunit alpha
Neutrophil cytochrome b 22 kDa polypeptide
Superoxide-generating NADPH oxidase light chain subunit
p22 phagocyte B-cytochrome
p22-phox
Short name=p22phox

Gene names

Name:

CYBA

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	195 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Critical component of the membrane-bound oxidase of phagocytes that generates superoxide. Associates with NOX3 to form a functional NADPH oxidase constitutively generating superoxide. Ref.10
Subunit structure	Composed of a heavy chain (beta) and a light chain (alpha). Interacts with SH3PXD2A By similarity. Interacts with DUOX1, DUOX2 and TPO. Interacts with NOX3 and NOX4. Interacts with calprotectin (S100A8/9). Ref.7 Ref.9 Ref.11 Ref.13
Subcellular location	Cell membrane Ref.8 Ref.13.
Post-translational modification	The heme prosthetic group could be coordinated with residues of the light chain, the heavy chain, or both, and it is possible that more than one heme is present per cytochrome b-245. Phosphorylation at Thr-147 enhances NADPH oxidase activity by promoting p47phox binding By similarity.
Involvement in disease	Granulomatous disease, chronic, cytochrome-b-negative, autosomal recessive (ARCGD) [MIM:233690]: A disorder characterized by the inability of neutrophils and phagocytes to kill microbes that they have ingested. Patients suffer from life-threatening bacterial/fungal infections. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21
Sequence similarities	Belongs to the p22phox family.

Ontologies

Keywords
Biological process	Electron transport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Chronic granulomatous disease Disease mutation
Ligand	Heme Iron Metal-binding NADP
Molecular function	Oxidoreductase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent Traceable author statement. Source: Reactome cellular response to amino acid stimulus Inferred from electronic annotation. Source: Compara cellular response to gamma radiation Inferred from electronic annotation. Source: Compara cellular response to glucose stimulus Inferred from electronic annotation. Source: Compara cellular response to mechanical stimulus Inferred from electronic annotation. Source: Compara cellular response to organic cyclic compound Inferred from electronic annotation. Source: Compara cellular response to tumor necrosis factor Inferred from electronic annotation. Source: Compara cytochrome complex assembly Inferred from direct assay PubMed 7938008. Source: BHF-UCL electron transport chain Inferred from electronic annotation. Source: UniProtKB-KW hydrogen peroxide biosynthetic process Inferred from sequence or structural similarity. Source: BHF-UCL inflammatory response Inferred from mutant phenotype Ref.5. Source: BHF-UCL innate immune response Inferred from mutant phenotype Ref.5. Source: BHF-UCL interaction with host Traceable author statement. Source: Reactome negative regulation of glomerular filtration by angiotensin Inferred from electronic annotation. Source: Compara oxidation-reduction process Inferred from mutant phenotype Ref.15Ref.5. Source: BHF-UCL phagosome maturation Traceable author statement. Source: Reactome positive regulation of cell growth Inferred from electronic annotation. Source: Compara positive regulation of endothelial cell proliferation Inferred from electronic annotation. Source: Compara respiratory burst Inferred from mutant phenotype Ref.5. Source: BHF-UCL response to drug Inferred from electronic annotation. Source: Compara response to interleukin-1 Inferred from electronic annotation. Source: Compara response to nutrient levels Inferred from electronic annotation. Source: Compara smooth muscle hypertrophy Inferred from sequence or structural similarity. Source: BHF-UCL superoxide anion generation Inferred from mutant phenotype Ref.5. Source: BHF-UCL
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: Compara NADPH oxidase complex Inferred from direct assay PubMed 3305576. Source: BHF-UCL apical plasma membrane Inferred from electronic annotation. Source: Compara dendrite Inferred from electronic annotation. Source: Compara mitochondrion Inferred from electronic annotation. Source: Compara neuronal cell body Inferred from electronic annotation. Source: Compara phagocytic vesicle membrane Traceable author statement. Source: Reactome secretory granule Traceable author statement PubMed 12005167. Source: BHF-UCL
Molecular_function	electron carrier activity Traceable author statement Ref.5. Source: UniProtKB heme binding Inferred from electronic annotation. Source: InterPro metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW oxidoreductase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NCF1	P14598	6	EBI-986058,EBI-395044

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.1

Chain

2 – 195

194

Cytochrome b-245 light chain

PRO_0000144907

Regions

Intramembrane

91 – 127

37

Compositional bias

133 – 189

57

Pro-rich

Sites

Metal binding

94

1

Iron (heme axial ligand) Potential

Amino acid modifications

Modified residue

147

1

Phosphothreonine By similarity

Natural variations

Natural variant

24

1

G → R in ARCGD. Ref.18 Ref.19 Ref.20
Corresponds to variant rs28941476 [ dbSNP | Ensembl ].

VAR_012755

Natural variant

25

1

G → V in ARCGD. Ref.18
Corresponds to variant rs179363891 [ dbSNP | Ensembl ].

VAR_060576

Natural variant

52

1

L → P in ARCGD. Ref.18
Corresponds to variant rs179363890 [ dbSNP | Ensembl ].

VAR_060577

Natural variant

53

1

E → V in ARCGD. Ref.16
Corresponds to variant rs179363893 [ dbSNP | Ensembl ].

VAR_060578

Natural variant

72

1

Y → H. Ref.1 Ref.6 Ref.22
Corresponds to variant rs4673 [ dbSNP | Ensembl ].

VAR_005122

Natural variant

90

1

R → Q in ARCGD. Ref.14

VAR_005123

Natural variant

90

1

R → W in ARCGD. Ref.18
Corresponds to variant rs179363892 [ dbSNP | Ensembl ].

VAR_060579

Natural variant

94

1

H → R in ARCGD. Ref.14

VAR_005124

Natural variant

118

1

S → R in ARCGD. Ref.5 Ref.18
Corresponds to variant rs104894514 [ dbSNP | Ensembl ].

VAR_005125

Natural variant

124

1

A → V in ARCGD. Ref.20
Corresponds to variant rs179363894 [ dbSNP | Ensembl ].

VAR_060580

Natural variant

125

1

A → T in ARCGD. Ref.21

VAR_060581

Natural variant

156

1

P → Q in ARCGD. Ref.15 Ref.17

VAR_005126

Natural variant

171

1

E → G. Ref.22
Corresponds to variant rs72667005 [ dbSNP | Ensembl ].

VAR_060582

Natural variant

174

1

V → A. Ref.1 Ref.2 Ref.4 Ref.6 Ref.22
Corresponds to variant rs1049254 [ dbSNP | Ensembl ].

VAR_054801

Natural variant

193

1

E → D. Ref.22

VAR_060583

Experimental info

Mutagenesis

157

1

P → Q: Loss of interaction with NOXO1. Ref.7

Secondary structure

1

.

.

.

195

Helix Strand Turn

Details...

Helix

161 – 165

5

Sequences

	Sequence		Length	Mass (Da)
	P13498 [UniParc]. Last modified November 2, 2010. Version 3. Checksum: 428427AD19398240	FASTA	195	21,013
	10 20 30 40 50 60 MGQIEWAMWA NEQALASGLI LITGGIVATA GRFTQWYFGA YSIVAGVFVC LLEYPRGKRK 70 80 90 100 110 120 KGSTMERWGQ KYMTAVVKLF GPFTRNYYVR AVLHLLLSVP AGFLLATILG TACLAIASGI 130 140 150 160 170 180 YLLAAVRGEQ WTPIEPKPRE RPQIGGTIKQ PPSNPPPRPP AEARKKPSEE EAAVAAGGPP 190 GGPQVNPIPV TDEVV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure and unique expression of the 22-kilodalton light chain of human neutrophil cytochrome b." Parkos C.A., Dinauer M.C., Walker L.E., Allen R.A., Jesaitis A.J., Orkin S.H. Proc. Natl. Acad. Sci. U.S.A. 85:3319-3323(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 2-26, VARIANTS HIS-72 AND ALA-174.
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-174.
[3]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-174. Tissue: Brain.
[5]	"Human neutrophil cytochrome b light chain (p22-phox). Gene structure, chromosomal location, and mutations in cytochrome-negative autosomal recessive chronic granulomatous disease." Dinauer M.C., Pierce E.A., Bruns G.A.P., Curnutte J.T., Orkin S.H. J. Clin. Invest. 86:1729-1737(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 12-123, VARIANT ARCGD ARG-118.
[6]	"Characterization of two monoclonal antibodies against cytochrome b558 of human neutrophils." Verhoeven A.J., Bolscher B.G., Meerhof L.J., van Zwieten R., Keijer J., Weening R.S., Roos D. Blood 73:1686-1694(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 51-195, VARIANTS HIS-72 AND ALA-174.
[7]	"Novel human homologues of p47phox and p67phox participate in activation of superoxide-producing NADPH oxidases." Takeya R., Ueno N., Kami K., Taura M., Kohjima M., Izaki T., Nunoi H., Sumimoto H. J. Biol. Chem. 278:25234-25246(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NOXO1, MUTAGENESIS OF PRO-157.
[8]	"Site-specific inhibitors of NADPH oxidase activity and structural probes of flavocytochrome b: characterization of six monoclonal antibodies to the p22phox subunit." Taylor R.M., Burritt J.B., Baniulis D., Foubert T.R., Lord C.I., Dinauer M.C., Parkos C.A., Jesaitis A.J. J. Immunol. 173:7349-7357(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, MEMBRANE TOPOLOGY.
[9]	"Identification of a novel partner of duox: EFP1, a thioredoxin-related protein." Wang D., De Deken X., Milenkovic M., Song Y., Pirson I., Dumont J.E., Miot F. J. Biol. Chem. 280:3096-3103(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DUOX1; DUOX2 AND TPO.
[10]	"The NADPH oxidase Nox3 constitutively produces superoxide in a p22phox-dependent manner: its regulation by oxidase organizers and activators." Ueno N., Takeya R., Miyano K., Kikuchi H., Sumimoto H. J. Biol. Chem. 280:23328-23339(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"Functional analysis of Nox4 reveals unique characteristics compared to other NADPH oxidases." Martyn K.D., Frederick L.M., von Loehneysen K., Dinauer M.C., Knaus U.G. Cell. Signal. 18:69-82(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NOX4.
[12]	"Phosphorylation of p22phox on threonine 147 enhances NADPH oxidase activity by promoting p47phox binding." Lewis E.M., Sergeant S., Ledford B., Stull N., Dinauer M.C., McPhail L.C. J. Biol. Chem. 285:2959-2967(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-147.
[13]	"Molecular interface of S100A8 with cytochrome b and NADPH oxidase activation." Berthier S., Nguyen M.V., Baillet A., Hograindleur M.A., Paclet M.H., Polack B., Morel F. PLoS ONE 7:E40277-E40277(2012) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH CALPROTECTIN.
[14]	"Cytochrome b558-negative, autosomal recessive chronic granulomatous disease: two new mutations in the cytochrome b558 light chain of the NADPH oxidase (p22-phox)." de Boer M., de Klein A., Hossle J.-P., Seger R., Corbeel L., Weening R.S., Roos D. Am. J. Hum. Genet. 51:1127-1135(1992) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ARCGD GLN-90 AND ARG-94.
[15]	"Point mutation in the cytoplasmic domain of the neutrophil p22-phox cytochrome b subunit is associated with a nonfunctional NADPH oxidase and chronic granulomatous disease." Dinauer M.C., Pierce E.A., Erickson R.W., Muhlebach T.J., Messner H., Orkin S.H., Seger R.A., Curnutte J.T. Proc. Natl. Acad. Sci. U.S.A. 88:11231-11235(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ARCGD GLN-156.
[16]	"Identification of allele-specific p22-phox mutations in a compound heterozygous patient with chronic granulomatous disease by mismatch PCR and restriction enzyme analysis." Hossle J.-P., de Boer M., Seger R.A., Roos D. Hum. Genet. 93:437-442(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ARCGD VAL-53.
[17]	"156Pro-->Gln substitution in the light chain of cytochrome b558 of the human NADPH oxidase (p22-phox) leads to defective translocation of the cytosolic proteins p47-phox and p67-phox." Leusen J.H., Bolscher B.G., Hilarius P.M., Weening R.S., Kaulfersch W., Seger R.A., Roos D., Verhoeven A.J. J. Exp. Med. 180:2329-2334(1994) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANT ARCGD GLN-156.
[18]	"Molecular analysis of 9 new families with chronic granulomatous disease caused by mutations in CYBA, the gene encoding p22(phox)." Rae J., Noack D., Heyworth P.G., Ellis B.A., Curnutte J.T., Cross A.R. Blood 96:1106-1112(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ARCGD ARG-24; VAL-25; PRO-52; TRP-90 AND ARG-118.
[19]	"Genetic studies of three Japanese patients with p22-phox-deficient chronic granulomatous disease: detection of a possible common mutant CYBA allele in Japan and a genotype-phenotype correlation in these patients." Yamada M., Ariga T., Kawamura N., Ohtsu M., Imajoh-Ohmi S., Ohshika E., Tatsuzawa O., Kobayashi K., Sakiyama Y. Br. J. Haematol. 108:511-517(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ARCGD ARG-24.
[20]	"Statistical and mutational analysis of chronic granulomatous disease in Japan with special reference to gp91-phox and p22-phox deficiency." Ishibashi F., Nunoi H., Endo F., Matsuda I., Kanegasaki S. Hum. Genet. 106:473-481(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ARCGD ARG-24 AND VAL-124.
[21]	"Characterization of six novel mutations in CYBA: the gene causing autosomal recessive chronic granulomatous disease." Teimourian S., Zomorodian E., Badalzadeh M., Pouya A., Kannengiesser C., Mansouri D., Cheraghi T., Parvaneh N. Br. J. Haematol. 141:848-851(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ARCGD THR-125.
[22]	"Three common polymorphisms in the CYBA gene form a haplotype associated with decreased ROS generation." Bedard K., Attar H., Bonnefont J., Jaquet V., Borel C., Plastre O., Stasia M.-J., Antonarakis S.E., Krause K.-H. Hum. Mutat. 30:1123-1133(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HIS-72; GLY-171; ALA-174 AND ASP-193.
+	Additional computationally mapped references.

Web resources

CYBAbase

CYBA mutation db

GeneReviews

SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M21186 mRNA. Translation: AAA90925.1.
BT006861 mRNA. Translation: AAP35507.1.
AC116552 Genomic DNA. No translation available.
BC006465 mRNA. Translation: AAH06465.1.
AH002664 Genomic DNA. Translation: AAA52134.1.

IPI

IPI00218433.

PIR

A28201.

RefSeq

NP_000092.2. NM_000101.3.

UniGene

Hs.513803.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WLP	NMR	-	A	149-167	[»]

ProteinModelPortal

P13498.

ModBase

Search...

Protein-protein interaction databases

IntAct

P13498. 5 interactions.

MINT

MINT-5209680.

STRING

9606.ENSP00000261623.

PTM databases

PhosphoSite

P13498.

Polymorphism databases

DMDM

311033459.

Proteomic databases

PaxDb

P13498.

PeptideAtlas

P13498.

PRIDE

P13498.

Protocols and materials databases

DNASU

1535.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000261623; ENSP00000261623; ENSG00000051523.

GeneID

1535.

KEGG

hsa:1535.

UCSC

uc002flb.3. human.

Organism-specific databases

CTD

1535.

GeneCards

GC16M088709.

H-InvDB

HIX0013335.

HGNC

HGNC:2577. CYBA.

HPA

CAB009492.

MIM

233690. phenotype.
608508. gene.

neXtProt

NX_P13498.

Orphanet

379. Chronic granulomatous disease.

PharmGKB

PA27075.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG39609.

HOGENOM

HOG000001585.

HOVERGEN

HBG051278.

InParanoid

P13498.

KO

K08009.

OMA

YPRGKRK.

OrthoDB

EOG44J2K8.

PhylomeDB

P13498.

Enzyme and pathway databases

Reactome

REACT_116125. Disease.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P13498.

Bgee

P13498.

CleanEx

HS_CYBA.

Genevestigator

P13498.

GermOnline

ENSG00000051523. Homo sapiens.

Family and domain databases

InterPro

IPR007732. Cyt_b558_asu.
[Graphical view]

PANTHER

PTHR15168. PTHR15168. 1 hit.

Pfam

PF05038. Cytochrom_B558a. 1 hit.
[Graphical view]

PIRSF

PIRSF019635. Cytochr_b558a. 1 hit.

ProtoNet

Search...

Other

ChEMBL

CHEMBL1613744.

ChiTaRS

CYBA. human.

EvolutionaryTrace

P13498.

GenomeRNAi

1535.

NextBio

6349.

SOURCE

Search...

Entry information

Entry name

CY24A_HUMAN

Accession

Primary (citable) accession number: P13498
Secondary accession number(s): Q14090, Q9BR72

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	November 2, 2010
Last modified:	May 1, 2013
This is version 135 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.